Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib (original) (raw)

Nature Genetics volume 37, pages 25–27 (2005)Cite this article

Abstract

Epigenetic defects in the imprinted GNAS cluster are associated with pseudohypoparathyroidism type Ib. In two kindreds with this disorder, we now report deletions that remove the differentially methylated region encompassing exon NESP55 and exons 3 and 4 of the antisense transcript. When inherited from a female, either deletion abolishes all maternal GNAS imprints and derepresses maternally silenced transcripts, suggesting that the deleted region contains a _cis_-acting element that controls imprinting of the maternal GNAS allele.

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Figure 1: GNAS and deletion of the NESP55 DMR in AD-PHP-Ib.

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Figure 2: Imprinting analysis of GNAS and NNAT.

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Imprinting disorders

Article 29 June 2023

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Acknowledgements

We thank H.M. Kronenberg and J.T. Lee for critically reviewing the manuscript. This work was funded, in part, by separate grants from National Institute of Diabetes and Digestive and Kidney Diseases (to M.B. and H.J.).

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Authors and Affiliations

  1. Department of Medicine, Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Murat Bastepe, Leopold F Fröhlich, Agnès Linglart, Hilal S Abu-Zahra & Harald Jüppner
  2. Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
    Katsuyoshi Tojo
  3. Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
    Leanne M Ward
  4. Pediatric Nephrology Unit, MassGeneral Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Harald Jüppner

Authors

  1. Murat Bastepe
  2. Leopold F Fröhlich
  3. Agnès Linglart
  4. Hilal S Abu-Zahra
  5. Katsuyoshi Tojo
  6. Leanne M Ward
  7. Harald Jüppner

Corresponding authors

Correspondence toMurat Bastepe or Harald Jüppner.

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The authors declare no competing financial interests.

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Bastepe, M., Fröhlich, L., Linglart, A. et al. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib.Nat Genet 37, 25–27 (2005). https://doi.org/10.1038/ng1487

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